Biodegradable, magnesium-containing bone screws, methods for their preparation and medical applications therefore

ABSTRACT

The invention relates to a biodegradable, magnesium-containing bone screw for implanting into a patient body for use in medical applications, such as, orthopedic, craniofacial and cardiovascular surgery. The bone screw has a head, shaft and tip. The thickness of the head is greater than the thickness of conventional bone screws. The shaft includes both a non-threaded and a threaded portion. The tip is non-threaded and pointed, such as, conical in shape. The composition of the bone screws provide for improved biodegradability and biocompatibility, and the features of the structure of the bone screws facilitate guidance and placement during implantation as well as reduce the potential for mechanical failures.

CROSS REFERENCE TO RELATED PATENT APPLICATIONS

This continuation patent application claims the benefit of priorityunder 35 U.S.C. § 120 from U.S. patent application Ser. No. 14/185,007filed Feb. 20, 2014, entitled “Biodegradable, Magnesium-Containing BoneScrews, Methods for Their Preparation and Medical ApplicationsTherefor,” now U.S. Pat. No. 10,849,667, which claims the benefit ofpriority under 35 U.S.C. § 119(e) from U.S. Provisional PatentApplication No. 61/767,812 entitled “Biodegradable, Magnesium-ContainingBone Screws, Methods for Their Preparation and Medical ApplicationsTherefor”, filed on Feb. 22, 2013, the contents of which areincorporated herein by reference.

GOVERNMENT SUPPORT AND FUNDING

The invention was made with government support under #0812348 awarded bythe National Science Foundation. The government has certain rights inthe invention.

FIELD OF THE INVENTION

The invention relates to biodegradable bone screws composed ofmagnesium-containing material, e.g., magnesium alloy, which are suitableas implant devices into a patient body for medical applications, suchas, orthopedic, craniofacial and cardiovascular surgery.

BACKGROUND OF THE INVENTION

Metallic implant devices, such as plates, screws, nails and pins,constructed of stainless steel, cobalt-chromium and titanium alloys arecommonly used in the practice of orthopedic, craniofacial andcardiovascular implant surgery. These materials exhibit goodbiomechanical properties, but are not degradable over a period of time.Thus, when the implant device is no longer needed, surgery is requiredfor its removal. To reduce the need for surgery and risks associatedtherewith, it is a desire in the art to design and develop newbiomaterials that are capable of degrading, e.g., dissolving, over timesuch that surgical removal is precluded. For example, polymers, such aspolyhydroxy acids, polylactic acid (PLA), polyglycolic acid (PGA), andthe like, are useful for the construction of implant devices. Thesematerials, however, have been found to exhibit relatively poor strengthand ductility, and have a tendency to react with human tissue resultingin limited bone growth. As a result, magnesium alloys have emerged as anew class of biodegradable materials for orthopedic applications. Thesematerials exhibit properties comparable to natural bone, are non-toxicand capable of degrading, e.g., corroding, over time in a physiologicalenvironment, e.g., a patient body. In particular, magnesium degrades toproduce a soluble, non-toxic corrosion hydroxide product which isharmlessly excreted through urine. To date, magnesium alloys havedemonstrated the ability to regenerate both hard and softmusculoskeletal tissues, which is particularly valuable for engineeringcraniofacial degradable implants.

There are, however, disadvantages associated with bone screws composedof magnesium-containing material, e.g., magnesium alloy. For example,magnesium is generally a softer material than metal materials, e.g.,stainless steel or titanium, conventionally used for implant devices. Asa result, magnesium alloy bone screws have been found to be more proneto breakage. In certain instances, during the process of implantation,the heads of the magnesium alloy screws have sheared off, and the screwshave been shown to be difficult to place in existing bone, e.g.,difficult to align with a corresponding opening which is drilled intoexisting tissue in a patient to receive the screw.

Thus, there is a need in the art to design and develop a bone screwhaving suitable corrosion resistance, biodegradability andbiocompatibility, while having an improved design structure so as tofacilitate alignment and placement of the screw, and to demonstrateminimal breakage, e.g., of the screw head, during implantation.

BRIEF DESCRIPTION OF THE DRAWINGS

A further understanding of the invention can be gained from thefollowing description of the preferred embodiments when read inconjunction with the accompanying drawings in which:

FIG. 1A is a side view of a bone screw in accordance with certainembodiments of the invention;

FIG. 1B is a top view of the bone screw of FIG. 1A in accordance withcertain embodiments of the invention;

FIG. 1C is a bottom view of the bone screw of FIG. 1A in accordance withcertain embodiments of the invention; and

FIG. 1D is a perspective view of the bone screw of FIG. 1A in accordancewith certain embodiments of the invention.

SUMMARY OF THE INVENTION

In an aspect of the invention, a biodegradable, magnesium-containingbone screw, is provided. The bone screw includes a head having a topsurface, a bottom surface and a thickness extending between the top andbottom surfaces; a shaft having a first end and a second end and alength linearly extending between the first and second ends; and anon-threaded, pointed tip extending from the second end of the shaft.The first end of the shaft is coupled to the bottom surface of the head.A portion of the length of the shaft extending from the first end to atransition point is non-threaded and a remaining portion of the lengthof the shaft extending from the transition point to the second end ofthe shaft is threaded. The thickness of the head is greater than aconventional bone screw head thickness.

The top surface of the head can include an indentation diametricallyformed therein. The indentation may have a length and height that issuitable to accommodate a driver mechanism for guiding and rotating thebone screw. The length of the indentation can extend along an entirediameter or nearly the entire diameter of the head.

In certain embodiments, the non-threaded portion of the length of theshaft is less than the threaded portion of the length of the shaft.Further, the tip may be cone-shaped.

The bone screw may be composed of magnesium alloy.

The bone screw may be employed as an implant device for medicalapplications. In certain embodiments, the bone screw is employed incraniofacial surgery.

In another aspect of the invention, a method of preparing abiodegradable, magnesium-containing bone screw is provided. The methodincludes preparing a magnesium-containing composition, melting themagnesium-containing composition at an elevated temperature, introducingthe melted magnesium-containing composition into a mold, cooling andsolidifying the mold. The mold includes a head having a top surface, abottom surface and a thickness extending between the top and bottomsurfaces, the thickness of the head being greater than a conventionalbone screw head thickness; a shaft having a first end and a second endand a length linearly extending between the first and second ends, thefirst end of the shaft coupled to the bottom surface of the head, aportion of the length of the shaft extending from the first end to atransition point being non-threaded and a remaining portion of thelength of the shaft extending from the transition point to the secondend of the shaft being threaded; and a non-threaded, pointed tipextending from the second end of the shaft.

In still another aspect of the invention, a method of employing abiodegradable screw as a medical device to regenerate new tissue in apatient is provided. The method includes preparing amagnesium-containing bone screw in accordance with the above-describedmethod, forming an opening in existing tissue in the patient, andimplanting the bone screw into the opening in the existing tissue of thepatient.

The existing tissue may be selected from craniofacial bone, orthopedicbone and cardiovascular tissue.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

The invention relates to novel, biodegradable bone screws constructedfrom magnesium-containing material, e.g., magnesium alloy, having animproved structure which is designed to facilitate alignment andplacement, and reduce breakage of the bone screw, e.g., the head of thebone screw, during implantation. These bone screws are suitable forimplanting into a body of a patient for medical applications, such asbut not limited to, orthopedic, craniofacial and cardiovascular surgery.

A wide variety of magnesium-containing materials, e.g., magnesiumalloys, may be employed to construct the biodegradable bone screws ofthe invention. Non-limiting examples of suitable materials include thosedescribed in PCT Application having International Application No.PCT/US2012/058939 entitled “Biodegradable Metal Alloys” filed on Oct. 5,2012 and based on U.S. Provisional Patent Application 61/544,127entitled “Biodegradable Metal Alloys” filed on Oct. 6, 2011; and U.S.Provisional Patent Application 61/710,338 entitled “BiodegradableIron-Containing Compositions, Methods of Preparing and ApplicationsTherefor” filed on Oct. 5, 2012, which are incorporated in theirentirety herein by reference.

In certain embodiments, the bone screws of the invention are constructedof a composition including magnesium and one or more of iron, zirconium,manganese, calcium, yttrium and zinc. For example, suitable compositionsinclude a combination, e.g., mixture or blend, of magnesium, iron,manganese and calcium, or a combination, e.g., mixture or blend, ofmagnesium, iron, zirconium and calcium, or a combination, e.g., mixtureor blend, of magnesium, iron zinc and calcium. The amount of each of thecomponents in the combinations/compositions can vary and in general, theamounts are selected such that the resulting combinations/compositionsare within acceptable non-toxic limits, sufficiently biocompatible anddegradable over a period of time. For example, the components and theiramounts may be selected such that the combinations/compositions exhibitcorrosion resistance in the presence of water and body fluids whichallow for suitable in-vitro use in a physiological environment, e.g.,patient body, and exhibit corrosion resistance with minimal or noevolution of hydrogen gas as the evolution of hydrogen, e.g., hydrogenbubbles, may cause complications in a patient body.

In certain embodiments, the composition for use in the inventionincludes from about 0.5 to about 4.0 weight percent of yttrium, fromgreater than zero to about 1.0 weight percent of calcium, from about0.25 to about 1.0 weight percent of zirconium, and the remainder orbalance being magnesium based on total weight of the composition. Inother embodiments, the composition includes from about 1.0 to about 6.0weight percent of zinc, from greater than zero to about 1.0 weightpercent of zirconium, and the remainder or balance being magnesium basedon total weight of the composition.

It is contemplated that other components may be added to thecompositions provided that the non-toxicity, biocompatibility anddegradability remain within acceptable limits. Acceptable non-toxiclimits and time frames for degradation can vary and can depend on theparticular physical and physiological characteristics of the patient,in-vitro site of implantation and medical use of the device.Non-limiting examples of suitable other components include aluminum,silver, cerium and/or strontium. In certain embodiments, each of thealuminum, silver, cerium and strontium may be present in an amount fromabout 1.0 to about 9.0 weight percent, from about 0.25 to about 1.0weight percent, from about 0.1 to about 1.0 weight percent and fromabout 1.0 to about 4.0 weight percent, respectively, based on totalweight of the composition.

In certain embodiments, the composition includes from about 0.5 to about4.0 weight percent of yttrium, from greater than zero to about 1.0weight percent of calcium, from about 0.25 to about 1.0 weight percentof silver, from about 0.25 to about 1.0 weight percent of zirconium, andthe remainder or balance being magnesium, based on total weight of thecomposition.

In other embodiments, the composition includes from about 0.5 to about4.0 weight percent of yttrium, from greater than zero to about 1.0weight percent of calcium, from about 0.1 to about 1.0 weight percent ofcerium, from about 0.25 to about 1.0 weight percent of zirconium, andthe remainder or balance being magnesium, based on total weight of thecomposition.

In other embodiments, the composition includes from about 0.5 to about4.0 weight percent of yttrium, from greater than zero to about 1.0weight percent of calcium, from about 0.25 to about 1.0 weight percentof silver, from about 0.1 to about 1.0 weight percent of cerium, fromabout 0.25 to about 1.0 weight percent of zirconium, and the remainderor balance being magnesium, based on total weight of the composition.

In yet other embodiments, the composition includes from about 1.0 toabout 6.0 weight percent of zinc, from about 0.25 to about 1 weightpercent of silver, from greater than zero to about 1.0 weight percent ofzirconium, and the remainder or balance being magnesium, based on totalweight of the composition.

In still other embodiments, the composition includes from about 1.0 toabout 6.0 weight percent of zinc, from about 0.1 to about 1 weightpercent of cerium, from greater than zero to about 1.0 weight percent ofzirconium, and the remainder or balance being magnesium, based on totalweight of the composition.

In still other embodiments, the composition includes from about 1.0 toabout 6.0 weight percent zinc, from about 0.25 to about 1 weight percentof silver, from about 0.1 to about 1 weight percent of cerium, fromgreater than zero to about 1.0 weight percent of zirconium, and theremainder or balance being magnesium, based on total weight of thecomposition.

Suitable compositions for use in the invention may be prepared usingvarious methods and processes. The components, e.g., magnesium and oneor more of iron, manganese, calcium, zirconium and zinc, may be meltedor alloyed at an elevated temperature using conventional methods knownin the art. In certain embodiments, the components are alloyed usinghigh energy mechanical alloying (HEMA), uniaxial or isostaticcompaction, and sintering. HEMA may be conducted under a protectiveatmosphere, e.g., in the presence of argon, sulfur hexafluoride andmixtures thereof, to preclude, minimize or reduce decomposition of thecomponents in the composition. Subsequent to HEMA, amorphous films maybe synthesized by pulsed laser deposition (PLD).

Further, it is known to use general casting methods and, forming andfinishing processes, such as, extrusion, forging, polishing (bymechanical and/or chemical means), surface treating (to form asuperficial layer), and combinations thereof, to produce the bone screwsof the invention for use as implant devices. For example, a moltenalloyed composition may be poured into a mold, allowed to cool andthereby solidify.

Suitable design structures for the bone screws can vary. In accordancewith the invention, the bone screws have a head, a shaft and a tip. Thehead has a top surface, a bottom surface and a thickness extendingbetween the top and bottom surfaces. The shape of the head, shaft andtip can vary. Typically, the head and shaft are cylindrical in shapesuch that the top and bottom surfaces of the head are circular. Further,as is typical with conventional screws, the diameter of the head isgreater than the diameter of the shaft. The thickness of the head isgreater than the thickness of a conventional bone screw head. The topsurface of the head has an indentation diametrically formed therein. Theindentation has a length and height that is suitable to accommodate adriver mechanism for rotating and guiding the bone screw. In certainembodiments, the length of the indentation extends along the entire ornearly the entire diameter of the top surface of the head. The shaft hasa first end and a second end and a length linearly extending between thefirst and second ends. The first end of the shaft is coupled to thebottom surface of the head. A first portion of the length of the shaftextends from the first end to a transition point. This first portion isnon-threaded. A remaining portion, e.g., second portion, of the lengthof the shaft extends from the transition point to the second end of theshaft. This second portion is threaded. In certain embodiments, thenon-threaded portion extends over a shorter length of the shaft ascompared to the length of the threaded portion. The tip is non-threaded,extends from the second end of the shaft and has a pointed end. Incertain embodiments, the tip is cone shaped.

FIG. 1A shows a side view of a bone screw 10 structure in accordancewith certain embodiments of the invention. In FIG. 1A, the bone screw 10includes a head 12, a shaft 14 and a tip 16. The head has a top surface12 a and a bottom surface 12 b. The shaft 14 has a first end 13 and asecond end 20. The head 12 is positioned at the first end 13 of theshaft 14 and the tip 16 is positioned at the second end 20 of the shaft.As shown, the top and bottom surfaces 12 a and 12 b of the head 12 havea circular shape. However, it is contemplated that the head surfaces 12a and 12 b can include various shapes. Further, as shown in FIG. 1B, thetop surface 12 a of the head 12 can have a diametrically positionedindentation 19 formed therein to accommodate a driver mechanism, such asa screw driver, (not shown) for rotating and guiding the bone screw 10.The shaft 14 includes a non-threaded region 15 and a threaded region 17.The non-threaded region 15 is adjacent to the head 12 and the threadedregion 17 is adjacent the tip 16. The non-threaded region 15 extendsfrom the first end 13 of the shaft 14 to the starting point of thethreaded region 17 and the threaded region 17 extends from the endingpoint of the non-threaded region 15 to the second end 20 of the shaft.The tip 16 is non-threaded, conical in shape and has a point 18 on itsend. It is contemplated that the point 18 facilitates insertion of thebone screw 10 into a patient's bone tissue (not shown).

The bone screws of the invention have a wider/taller or thicker headthan conventional bone screws known in the art. As shown in FIG. 1A, thehead 12 has a thickness T and as shown in FIG. 1B, a diameter DH. Incertain embodiments, the thickness T can be from about 0.96 mm to about1.04 mm or about 1.0 mm and the diameter DH can be from about 1.92 mm toabout 2.08 mm or about 2.0 mm. Further, as shown in FIG. 1A, the shaft14 and tip 16 have a combined length L1. In certain embodiments, thelength L1 can be from about 2.58 mm to about 2.80 mm or about 2.69 mm.Also, as shown in FIG. 1A, a length L2 represents the combined length ofthe threaded region 17 and the tip 16. In certain embodiments, thelength L2 can be from about 2.32 mm to about 2.52 mm or about 2.42 mm.As for diameter DS of the shaft 14, as is generally indicative ofscrews, the diameter DS is less than the diameter DH of the head 12 (asshown in FIG. 1C). In certain embodiments, the diameter DS can be fromabout 0.96 mm to about 1.04 mm or about 1.0 mm. Furthermore, as shown inFIG. 1B, the length of the indentation 19 is LI and its width is W. Incertain embodiments, the width W can be from about 0.48 to about 0.52 mmor about 0.50 mm. In certain embodiments, the length LI can be equal tothe diameter DH or nearly equal to DH. The height H of the indentation19 is shown in FIG. 1D. In certain embodiments, the height H can be fromabout 0.48 mm to about 0.52 mm or about 0.50 mm. In certain embodiments,the length of the non-threaded portion NL can be from about 0.26 mm toabout 0.28 mm or about 0.27 mm. In certain embodiments, the length ofthe threaded portion TL can be from about 1.84 mm to about 2.00 mm orabout 1.92 mm. In certain embodiments, the length of the tip LP, asshown in FIG. 1A, can be from about 0.48 mm to 0.52 mm or about 0.5 mm.

Without intending to be bound by any particular theory, it is believedthat the biodegradable bone screws according to the invention have oneor more of the following advantages as compared to conventional bonescrews known in the art:

-   -   (i) The use of a biodegradable magnesium-containing material or        magnesium alloy material eliminates the need for surgery to        remove the screws from the patient;    -   (ii) The enlarged head size and an adjacent non-threaded region        of the shaft allows the screw to withstand the needed torque        applied to the head of the screw during implantation into a        bone; and    -   (iii) The non-threaded tip disposed at the distal portion of the        shaft allows for better guidance into the bone of the patient.

In certain embodiments, the bone screws of the invention are implantedinto a patient body by forming one or more openings in existing tissueand inserting or implanting the bone screws within the opening(s). Incertain embodiments, the bone screws are effective to regenerate tissue.

EXAMPLES

Bone screws were fabricated from commercially available pure Mg and a Mgaluminum zinc alloy (AZ31) purchased from Goodfellow (Oakdale, Pa.). Thepure Mg was 99.9% pure, and the AZ31 alloy contained 2.5-3.5 wt %aluminum, 0.6-1.4 wt % zinc, and 0.2-1.0 wt % manganese with theremainder being Mg. Similarly sized, commercially available stainlesssteel screws were purchased from Small Parts (Seattle, Wash.) forcomparison.

For in-vitro analysis, a mechanical test was designed to compare theholding strength of the pure Mg and AZ31 screws to stainless steelscrews. A material testing system was set up for complete axial pull-outtests (MTS Insight, MTS Systems, Eden Prairie, Minn.). Synthetic bonemade of solid rigid polyurethane foam (ASTM F-1839-08) from Sawbones (adivision of Pacific Research Laboratories, Inc. Vashon, Wash.) was usedas the control material for the pull-out tests. Screws were placed inthe foam after the holes were predrilled and tapped. A testing rate of 5mm/min was used according to ASTM standard F543-07. The maximum forceneeded to release the screw from the foam was recorded for each screw.Pure Mg and AZ31 screws exhibited pull-out forces similar to that forthe stainless steel screws when pulled out of a synthetic bone material.The pull-out strength for all of these screw materials was approximately40 N with no statistically significant differences between the groups.

For in-vivo analysis, the pure Mg and AZ31 screws were implanted in atleast three different rabbits' mandibles for each time point of 4, 8,and 12 weeks. The screws were implanted in the mandible near theincisure of facial vessels, located where the curve of the mandible andthe posterior end of the molar region meet. Two screws of the samematerial were placed in predrilled holes on one side of the mandible.Two screws of another material were placed on the opposite side of themandible using the same procedure. Screw types were not mixed on a perside basis to avoid galvanic corrosion. The control rabbits wereimplanted and incubated for 12 weeks. The control groups included agroup with stainless steel screws implanted, and a group where osteomies(holes) were drilled into the mandible but no screws were placed. Naïvecontrol bone was also examined. MicroCT (computed tomography) was usedto assess bone remodeling and Mg-alloy degradation, both visually andqualitatively through volume fraction measurements for all time points.Histologic analysis was also completed for the Mg and AZ31 screws at 12weeks, samples were formalin fixed, embedded in plastic, sectioned, andstained with hematoxylin and eosin. For the control samples, after 12weeks, the mandibles with holes and without screws showed many signs ofremodeling. The original holes were not apparent, and new bone growthwas seen throughout the region where the holes existed. When compared tonaïve control bone, the remodeled bone appeared to be rougher andthicker. After 12 weeks, the stainless steel screws were fully intact.Bone growth occurred around the stainless steel screws, but growth overthe screws and bone resorption under the screws were not observed. At 4weeks, the pure Mg screws were in contact with the bone. Then at 8 weeksthe shafts of the pure Mg screws appeared to be mostly degraded, as seenby the presence of holes within the screw bulk in the images, as well asmajor bone resorption with little new bone formation around the screws.By 12 weeks, the bone resorption seemed to subside, and new boneappeared to be growing over the pure Mg screw in 71% of the screwsimaged from both sets of scans, while at the same time bone resorptionunder the head of the screw was still noted in approximately 85% of thepure Mg screws. The AZ31 screws showed little sign of degradation at 4weeks, and the surrounding tissue seemed to remain intact. At 8 weeks,the AZ31 screws began to show signs of degradation, with regions ofreduced brightness appearing in the shaft region of the screws. Theadjacent tissue continued to remodel around the screw, as seen by somenew bone growth around the screws, and little bone resorption. At 12weeks, the AZ31 screws continued to show signs of degradation with alarger area of decreased brightness in the shaft of the screw. Thesurrounding tissue continued to remodel and grow around the screws. Fromboth sets of scans, there were signs of bone resorption under the headof the screw in approximately 71% of the cases at 12 weeks. Bone grewaround and over the head of the AZ31 screws in approximately 57% of thecases for the AZ31 screws at 12 weeks. Histology confirmed the findingsnoted in the microCT images for pure Mg and AZ31 groups at 12 weeks,identifying the brighter areas around the screws on the images as newlyformed bone. The results showed that craniofacial bone remodelingoccurred around both Mg-alloy screw types. Pure Mg had a differentdegradation profile than AZ31, however bone growth occurred around bothscrew types. The degradation rate of both pure Mg and AZ31 screw typesin the bone marrow space and the muscle were faster than in the corticalbone space at 12 weeks.

Several different designs of magnesium bone screws were tested in-vitroand in-vivo to assess the ease of implantation and probability offailure. A set of first generation screws had a design structure whichdiffered from certain embodiments of the invention in that each had ashort (or thin) head portion, a flat tip and threading that extended theentire length of the shaft. In comparison, the bone screws according tothe invention, a set of third generation screws, had a taller (orthicker) head portion, a pointed tip and threading that did not extendthe entire length of the shaft to the head of the screw. The firstgeneration screws were tested in-vitro by drilling holes in excisedrabbit mandible bone and inserting the screws in the pre-drilled holes.The results showed that 4 out of 19 failed because the head of the screwwas sheared off. Further, it was found that alignment of these screwswith the pre-drilled holes was difficult. The third generation screwswere also tested in-vitro by drilling holes in excised rabbit mandiblebone and inserting the screws in the pre-drilled holes. The resultsshowed that 0 out of 15 failed. The first generation screws, the thirdgeneration screws and second generation screws were then tested in-vivo.The second generation screws had a design which included a taller (orthicker) head portion than the first generation screws, a pointed tipand threading that extended the entire length of the shaft. The in-vivotest results showed that the first generation screws failed in 3 out of4 attempts. The in-vivo failures of the first generation screws occurreddue to their inability to be aligned with the pre-drilled holes, i.e.,the surgeon was not able to align the screws with the pre-drilled holesin the rabbit mandible. In the in-vivo tests for the second generationscrews, problems occurred with the head shearing off the screws in 2 outof 5 attempts. However, with the second generation screws, the pointedtip allowed for ease of alignment in-vivo as compared to the difficultyin aligning the flat tip of the first generation screws. When the thirdgeneration screws were implanted, only 5 out of 41 in-vivo attemptsfailed due to the head being sheared off. Based on the total number ofin-vitro and in-vivo tests conducted, the results showed that only 5 outof 56 third generation screws failed compared to 7 out of 23 firstgeneration screws and 2 out of 5 second generation screws.

While specific embodiments of the invention have been described indetail, it will be appreciated by those skilled in the art that variousmodifications and alternatives to those details could be developed inlight of the overall teachings of the disclosure. Accordingly, theparticular embodiments disclosed are meant to be illustrative only andnot limiting as to the scope of the invention which is to be given thefull breadth of the appended claims and any and all equivalents thereof.

We claim:
 1. A method of preparing a biodegradable bone screw,comprising: preparing a magnesium-based alloy; melting themagnesium-based alloy to form a melted magnesium-based alloy;introducing the melted magnesium-based alloy into a mold, the moldcomprising; a cylindrical head having a top surface, a bottom planarsurface, and a thickness extending between the top surface and bottomplanar surface; a pointed tip; a cylindrical shaft extending outwardlyfrom the bottom planar surface of the cylindrical head, comprising: acircumference; a first end connected to the cylindrical head; a secondend connected to the pointed tip; a length extending along a linearsurface of the shaft between the first and second ends, comprising: acontinuous non-threaded region; a circumferentially continuous threadedregion comprising threads disposed about the circumference of thecylindrical shaft; and a transition point, wherein the continuousnon-threaded region extends along an entirety of the length from thefirst end to the transition point, and the continuous threaded regionextends along an entirety of the length from the transition point to thesecond end; and cooling and solidifying the magnesium-based alloy tohave the shape of the mold.
 2. A method of employing a biodegradablebone screw to regenerate new tissue in a patient, comprising: preparinga biodegradable bone screw in accordance with claim 1; and positioningthe biodegradable bone screw as a medical implant device.
 3. The methodof claim 2, wherein the positioning comprises: forming an opening intissue of the patient; and implanting the biodegradable bone screw intothe opening.
 4. The method of claim 2, wherein the medical implantdevice is selected from the group consisting of a craniofacial boneimplant, an orthopedic bone implant and a cardiovascular tissue implant.5. The method of claim 1, wherein the preparing comprises a processselected from the group consisting of high energy mechanical alloying,uniaxial and isostatic compaction, and sintering.
 6. The method of claim5, wherein the high energy mechanical alloying is conducted under aprotective atmosphere.
 7. The method of claim 6, wherein the protectiveatmosphere is effective to preclude, minimize or reduce decomposition ofthe magnesium-based alloy.
 8. The method of claim 6, wherein theprotective atmosphere comprises at least one component selected from thegroup consisting of argon, sulfur hexafluoride and mixtures thereof. 9.The method of claim 5 wherein subsequent to the high energy mechanicalalloying, amorphous films are synthesized by pulsed laser deposition.10. The method of claim 5, further comprising one or more processesselected from the group consisting of casting, forming and finishing.11. The method of claim 10 wherein the forming is selected from thegroup consisting of extrusion and forging, and the finishing is selectedfrom the group consisting of mechanical polishing, chemical polishing,and surface treating.
 12. The method of claim 1, wherein themagnesium-based alloy, comprises: from about 0.5 to about 4.0 weightpercent yttrium; from greater than 0 to about 1.0 weight percentcalcium; from about 0.25 to about 1.0 weight percent zirconium; and aremainder of magnesium.
 13. The method of claim 1, wherein themagnesium-based alloy, comprises: from about 1.0 to about 6.0 weightpercent zinc; from greater than 0 to about 1.0 weight percent zirconium;and a remainder of magnesium.
 14. The method of claim 12, wherein themagnesium-based alloy further comprises one or more element selectedfrom the group consisting of aluminum, silver, cerium and strontium. 15.The method of claim 13, wherein the magnesium-based alloy furthercomprises one or more element selected from the group consisting ofaluminum, silver, cerium and strontium.
 16. A method of remodelingtissue in a patient, comprising: preparing a magnesium componentselected from the group consisting of magnesium and magnesium-basedalloy; melting the magnesium component to form a melted magnesiumcomponent; introducing the melted magnesium component into a mold, themold comprising; a cylindrical head having a top surface, a bottomplanar surface, a diameter, and a thickness extending between the topsurface and bottom planar surface; a pointed tip; a cylindrical shaftextending outwardly from the bottom planar surface of the cylindricalhead, comprising: a circumference; a first end connected to thecylindrical head; a second end connected to the pointed tip; a lengthextending along a linear surface of the shaft between the first andsecond ends, comprising: a continuous non-threaded region; acircumferentially continuous threaded region comprising threads disposedabout the circumference of the cylindrical shaft; and a transitionpoint, wherein the continuous non-threaded region extends along anentirety of the length from the first end to the transition point, andthe continuous threaded region extends along an entirety of the lengthfrom the transition point to the second end; and cooling and solidifyingthe magnesium-based alloy to have the shape of the mold.
 17. The methodof claim 16, wherein the thickness is about 1.0 mm and the diameter isfrom about 1.92 mm to about 2.08 mm or about 2.0 mm.